1. Field of the Invention
The present invention relates to a method for treating or preventing locally periodontal disease. In particular, the present invention relates to a method for treating or preventing periodontal disease which comprises administering ofloxacin (9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid) or salts thereof to periodontal tissue of a patient having periodontal disease.
2. Description of the Prior Art
Periodontal disease and dental caries are the two most common diseases in the dental field. In most cases, tooth loss in adults is caused by periodontal disease. Periodontal disease is an inflammatory disease on periodontal tissue such as the gingiva, and includes various types which vary depending on the progress degree of the disease or the age of the patient. Generally, those types can be mainly classified into gingivitis and periodontitis. Further, periodontitis can be classified into adult periodontitis and juvenile periodontitis.
Previously, it was hypotherized that periodontal disease was caused by non-specific stimulation derived from dental calculus or dental plaque. However, recent intensive bacteriological and immunochemical investigation have made it apparent that some specific bacteria among more than 200 kinds of bacteria, which exist in the dental plaque, relate to the occurrence of periodontal disease.
Particularly, as those bacteria, Actionmyces group, Spirochetes group, and gram negative bacteria such as Bacteroides group, Actinobacillus group, Fusobacterium group, Capnocytophaga group, Eikenella group are noted.
Further, relationships between some bacteria and some periodontal diseases have been reported. For example, Bacteroides gingivalis is supposed to relate to occurrence of adult periodontitis and Actinobacillus actinomycetemcomitans is supposed to relate to occurrence of juvenile periodontitis.
Periodontal disease has been treated by the following methods;
(1) Scaling for the purpose of removing sub-gingival plaque and dental calculus from periodontal pockets,
(2) Gingivectomy for the purpose of removing the inflammatory tissue or periodontal pocket, and,
(3) Root planning for the purpose of mechanically grinding the surface of the dental roots to accelerate the adhesion of the gingiva on the dental roots.
These methods are effective to some extent. However, some patients with specific internal diseases, for example a circulatory disease cannot undergo those surgical operations.
Further, as treating agents for periodontal disease, dentifrices containing a germicide or antiinflammatory agent, and pastes for massaging the gingiva have been used. However, these agents are not yet satisfactory for the treatment of periodontal disease. Under these circumstances, a method for treating periodontal disease, which is more effective than hose mechanical or surgical methods, is strongly desired.
As described above, specific bacteria relate to the occurrence of periodontal disease. Therefore, it is supposed to be effective for the treatment of periodontal disease to apply an antibacterial agent such as antibiotics in a suitable form to treat at an effective concentration the lesions of periodontal disease. However, this method has not been conducted for the following reasons:
(i) The bacteria which cause periodontal disease have not been identified. PA1 (ii) Periodontal disease is usually classified into a chronic inflammatory disease and, it takes a long time to treat that disease. Therefore, when an antibacterial agent is given over a long period, a side effect of the agent may appear, or an opportunistic infection may appear by a disturbance of normal bacterial flora in the oral cavity and intestines. PA1 (iii) No suitable administration method has been proposed. The bacteria which cause periodontal disease exists in the periodontal pockets between the teeth and the gingiva. Since the pockets are anatomically outer parts of the body, antibacterial agents are not delivered effectively to them when it is administered orally or by injection. Furthermore, even when they are administered in the form of a dentifrice, mouth wash or gingival massaging agent, they are not substantially delivered to the periodontal pockets and further, they are removed rapidly by the washing effect of saliva. Therefore, an effective concentration of antibacterial agents in the lesions of periodontal disease cannot be maintained.
After intensive investigations to solve these problems, the inventors have found that ofloxacin or salts thereof exhibit strong antibacterial effects against those bacteria and that when they are administered locally to lesions of periodontal disease, specifically to the periodontal pockets, remarkable effects on the treatment of periodontal disease are obtained.